Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование
The Effect of Atypical Antipsychotic Drugs on the Neurotrophic Factors Gene Expression in the MPTP Model of Parkinson's Disease. / Tsybko, A. S.; Il'chibaeva, T. V.; Khotskin, N. V. и др.
в: Neurochemical Journal, Том 13, № 2, 04.2019, стр. 169-175.Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование
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TY - JOUR
T1 - The Effect of Atypical Antipsychotic Drugs on the Neurotrophic Factors Gene Expression in the MPTP Model of Parkinson's Disease
AU - Tsybko, A. S.
AU - Il'chibaeva, T. V.
AU - Khotskin, N. V.
AU - Kovetskaya, A. I.
AU - Naumenko, V. S.
AU - Popova, N. K.
PY - 2019/4
Y1 - 2019/4
N2 - Atypical antipsychotics (AAP) are used in the therapy of Parkinson's disease (PD) for elimination of psychotic symptoms. As the brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF) and cerebral dopamine neurotrophic factor (CDNF) play a crucial role in the PD treatment, the aim of our study was the investigation of the effects of chronic treatment with commonly used AAP, clozapine and quetiapine, on the motor behavior and the BDNF, GDNF and CDNF genes expression in the mouse brain in the PD model produced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Clozapine and quetiapine (1 mg/kg, i.p.) were administered 48 hours after the last MPTP injection, and treatment continued for the following 16 days. Then animals were euthanized, substantia nigra (SN), striatum (St) and hippocampus (Hc) were extracted for RT-PCR and tyrosine hydroxylase (TH) western blot assessment. MPTP treatment led to 50% depletion in the TH protein level in the St. MPTP caused significant decrease in both BDNF and GDNF mRNA level in the Hc and St, respectively. At the same time, increase in the GDNF expression in the MPTP + clozapine group in the SN was found. MPTP caused dramatic decrease in the CDNF mRNA level in the SN with simultaneous increase in the St. Both clozapine and quetiapine decreased it to a normal level in the St. The effect of AAP clozapine and quetiapine on the GDNF and CDNF genes expression in the pharmacological model of PD has been shown for the first time.
AB - Atypical antipsychotics (AAP) are used in the therapy of Parkinson's disease (PD) for elimination of psychotic symptoms. As the brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF) and cerebral dopamine neurotrophic factor (CDNF) play a crucial role in the PD treatment, the aim of our study was the investigation of the effects of chronic treatment with commonly used AAP, clozapine and quetiapine, on the motor behavior and the BDNF, GDNF and CDNF genes expression in the mouse brain in the PD model produced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Clozapine and quetiapine (1 mg/kg, i.p.) were administered 48 hours after the last MPTP injection, and treatment continued for the following 16 days. Then animals were euthanized, substantia nigra (SN), striatum (St) and hippocampus (Hc) were extracted for RT-PCR and tyrosine hydroxylase (TH) western blot assessment. MPTP treatment led to 50% depletion in the TH protein level in the St. MPTP caused significant decrease in both BDNF and GDNF mRNA level in the Hc and St, respectively. At the same time, increase in the GDNF expression in the MPTP + clozapine group in the SN was found. MPTP caused dramatic decrease in the CDNF mRNA level in the SN with simultaneous increase in the St. Both clozapine and quetiapine decreased it to a normal level in the St. The effect of AAP clozapine and quetiapine on the GDNF and CDNF genes expression in the pharmacological model of PD has been shown for the first time.
KW - clozapine
KW - quetiapine
KW - BDNF
KW - GDNF
KW - CDNF
KW - MPTP
KW - DOPAMINE RELEASE
KW - SUBSTANTIA-NIGRA
KW - BDNF EXPRESSION
KW - MOUSE MODEL
KW - QUETIAPINE
KW - HIPPOCAMPUS
KW - SEROTONIN
KW - PSYCHOSIS
KW - BEHAVIOR
U2 - 10.1134/S1819712419020120
DO - 10.1134/S1819712419020120
M3 - Article
VL - 13
SP - 169
EP - 175
JO - Neurochemical Journal
JF - Neurochemical Journal
SN - 1819-7124
IS - 2
ER -
ID: 23291862